Rogers S A, Karl I E, Hammerman M R
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Am J Physiol. 1989 Nov;257(5 Pt 1):E751-6. doi: 10.1152/ajpendo.1989.257.5.E751.
To characterize the action of growth hormone (GH) on gluconeogenesis in renal proximal tubule, glucose production was measured in suspensions of canine renal proximal tubular segments incubated with 1 mM L-alanine, 10 mM lactate, 1 mM succinate, and various concentrations (10(-11) to 10(-6) M) of recombinant bovine GH (bGH). Production of glucose increased as a function of time for 120 min. Bovine growth hormone (10(-6) M) increased glucose production at 120 min by 55 +/- 16%. Significant enhancement of glucose production occurred in suspensions of segments incubated with as little as 10(-10) M bGH. Half-maximal stimulation occurred at between 10(-9) and 10(-8) M. To ascertain whether these actions of bGH are mediated directly, we determined the effects of insulin-like growth factors (IGFs) I and II on glucose production. Addition of IGF-I to segments enhanced glucose production in a concentration-dependent manner. However, incubation with bGH did not induce measurable IGF-I production in the segments. In contrast to the action of IGF-I, IGF-II did not affect glucose production. We conclude that bGH acts directly on cells within proximal tubular segments to enhance gluconeogenesis. Stimulation of gluconeogenesis in vitro could reflect a counterregulatory action of GH exerted on renal proximal tubule in vivo.
为了表征生长激素（GH）对肾近端小管糖异生作用，在与1 mM L-丙氨酸、10 mM乳酸、1 mM琥珀酸以及不同浓度（10⁻¹¹至10⁻⁶ M）重组牛生长激素（bGH）孵育的犬肾近端小管节段悬浮液中测量葡萄糖生成。葡萄糖生成随时间增加，持续120分钟。牛生长激素（10⁻⁶ M）使120分钟时的葡萄糖生成增加55±16%。在与低至10⁻¹⁰ M bGH孵育的节段悬浮液中，葡萄糖生成显著增强。半数最大刺激发生在10⁻⁹至10⁻⁸ M之间。为确定bGH的这些作用是否直接介导，我们测定了胰岛素样生长因子（IGFs）I和II对葡萄糖生成的影响。向节段中添加IGF-I以浓度依赖方式增强葡萄糖生成。然而，与bGH孵育并未在节段中诱导可测量的IGF-I生成。与IGF-I的作用相反，IGF-II不影响葡萄糖生成。我们得出结论，bGH直接作用于近端小管节段内的细胞以增强糖异生。体外糖异生的刺激可能反映了GH在体内对肾近端小管施加的一种反调节作用。
